A lupus anticoagulant (LA) is an autoantibody that inhibits a phospholipid-dependent coagulation reaction. LA is detected in a patient with antiphospholipid antibody syndrome that exhibits thrombosis and pregnancy complications. Since LA inhibits phospholipids required for a phospholipid-dependent coagulation reaction, coagulation time is prolonged in the blood of an LA-positive patient. On the other hand, coagulation time is prolonged even in the blood of a patient who received an anticoagulant such as warfarin. Therefore, in order to accurately detect a blood specimen of an LA-positive patient, it is necessary to discriminate a blood specimen containing LA and a blood specimen containing an anticoagulant. However, it is difficult to distinguish between the two in a normal coagulation test.
In the case where the subject is suspected of being LA positive, a mixing test is performed as a test of LA. In the mixing test, plasma of a subject and normal plasma are mixed, and the coagulation time of the obtained mixed plasma is measured. When the subject is an LA-positive patient, prolongation of coagulation time is not improved even when a mixing test is performed. Furthermore, an index for quantitatively evaluating the result of the mixing test such as ICA (Index of Circulating Anticoagulant) or LR (Lupus Ratio) value is calculated from the coagulation time of the plasma of a subject, normal plasma and mixed plasma, and a method of detecting LA based on this index is also known. Also, in the confirmatory test of LA, it is confirmed whether prolongation of coagulation time depends on phospholipid. Specifically, the coagulation time is measured using two kinds of coagulation time measurement reagents having different concentrations of phospholipids, and based on the ratio of the coagulation time obtained from each reagent, prolongation of the coagulation time dependent on the phospholipid concentration is confirmed to detect a specimen containing LA. For example, US 2004/091952 describes that a specimen containing LA and a specimen containing warfarin could be discriminated by combining a mixing test and a phospholipid dependent confirmatory test. Specifically, the coagulation times of mixed plasma and normal plasma were measured using two kinds of coagulation time measurement reagents having different concentrations of phospholipids, and the LR values calculated from these coagulation times were used to discriminate plasma of LA-positive patients and plasma of patients who received warfarin.
Conventionally, warfarin is often used as an anticoagulant. Warfarin, also called vitamin K antagonist, inhibits vitamin K necessary for the production of coagulation factors, thereby suppressing the formation of coagulation factors in the liver and exhibiting an anticoagulation effect. In recent years, novel anticoagulants with an action mechanism different from warfarin are also used. Such an anticoagulant exhibits an action of binding to a coagulation factor and directly inhibiting the coagulation reaction mediated by the coagulation factor. Hereinafter, the anticoagulant having an action of directly inhibiting a coagulation reaction is also referred to as “direct anticoagulant” or “DAC”. Coagulation time is prolonged even in the blood of a patient who received DAC. When the blood specimen of the subject who received DAC was determined to be a specimen containing LA by mistake, excessive anticoagulation therapy may be given to the subject. Excessive anticoagulation therapy increases the risk of bleeding. Therefore, discrimination between blood specimens containing LA and blood specimens containing DAC is clinically important. However, it has been difficult to make such discrimination by conventional methods. Therefore, it is desirable to develop means capable of discriminating a blood specimen containing LA and a blood specimen containing DAC.